Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Org Lett. 2020 May 1;22(9):3313-3317. doi: 10.1021/acs.orglett.0c00474. Epub 2020 Mar 17.
Total synthesis of (-)-lepadiformine A featuring construction of the 1-azaspiro[4.5]decane skeleton by a highly diastereoselective radical translocation-cyclization reaction of a γ-lactam derivative bearing a chiral butenolide moiety is described. The enantioselective construction of butenolide is conducted via Krische's catalytic asymmetric allylation protocol. After the radical translocation-cyclization reaction, a hydroxymethyl group at the C-13 position was stereoselectively introduced by a one-pot partial reduction-allylation protocol of the unprotected lactam derivative. Finally, the total synthesis is completed by formation of a C ring.
本文描述了通过带有手性丁烯内酯部分的γ-内酰胺衍生物的高非对映选择性自由基迁移-环化反应构建 1-氮杂螺[4.5]癸烷骨架，实现了（-）-lepadiformine A 的全合成。丁烯内酯的对映选择性构建是通过 Krische 的催化不对称烯丙基化反应来完成的。在自由基迁移-环化反应之后，通过未保护的内酰胺衍生物的一锅法部分还原-烯丙基化反应，在 C-13 位立体选择性地引入了羟甲基基团。最后，通过 C 环的形成完成了全合成。
